Short- and long-term efficacy of aspirin and clopidogrel for thromboprophylaxis for mechanical heart valves: an in vivo study in swine.
OBJECTIVE
In the interest of exploring alternatives to warfarin, we tested the hypothesis that clopidogrel combined with aspirin is effective for thromboprophylaxis of mechanical valves using a swine model.


METHODS
Adult swine underwent heterotopic implantation of a modified bileaflet mechanical valved conduit bypassing the ligated, native descending thoracic aorta. Animals were randomized to no anticoagulation (n = 7), 175 U/kg dalteparin administered subcutaneously twice daily (n = 9), 325 mg of aspirin (n = 6), 75 mg of clopidogrel (n = 6), or 325 mg of aspirin and 75 mg of clopidogrel daily (n = 6) and survived for 30 days. Additionally, 11 animals were randomized to no anticoagulation (n = 5) or 325 mg of oral aspirin and 75 mg of clopidogrel daily (n = 6) and survived for 150 days.


RESULTS
At 30 days, we observed 216 +/- 270 mg of thrombus for the no anticoagulation group, 53 +/- 91 mg for the dalteparin group, 33 +/- 23 mg for the aspirin group, 25 +/- 10 mg for the clopidogrel group, and 17 +/- 9 mg for the combined aspirin and clopidogrel group, respectively (P < .01 for clopidogrel and aspirin vs no anticoagulation). At 150 days, we observed 223 +/- 200 mg of thrombus for the no anticoagulation group and 4 +/- 4 mg for the aspirin and clopidogrel group (P = .02). Mean platelet deposition on the valve was 4.1 x 10(9) +/- 3.6 x 10(9) for the no anticoagulation and 6.81 x 10(7) +/- 1.4 x 10(8) for the combined aspirin and clopidogrel groups, respectively (P = .03). No major hemorrhagic events were observed.


CONCLUSIONS
Effective short- and long-term thromboprophylaxis of mechanical valves can be achieved by using dual-antiplatelet therapy in this porcine model. Prospective human trials should be conducted with combination aspirin and clopidogrel as an alternative to warfarin in patients with bileaflet mechanical aortic valves.
McKellar
Stephen H
SH
Division of Cardiovascular Surgery, Mayo Clinic, Rochester, Minnesota 55905, USA.
Thompson
Jess L
JL
Garcia-Rinaldi
Raul F
RF
Macdonald
Ryan J
RJ
Sundt
Thoralf M
TM
Schaff
Hartzell V
HV
D000284:Administration, Oral; D000818:Animals; D001241:Aspirin / Q000494:pharmacology*; D001705:Bioprosthesis; D000077144:Clopidogrel; D017985:Dalteparin / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D019918:Heart Valve Prosthesis Implantation / Q000009:adverse effects / Q000379:methods*; D007279:Injections, Subcutaneous; D011182:Postoperative Care; D011183:Postoperative Complications / Q000517:prevention & control; D011897:Random Allocation; D012307:Risk Factors; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric; D015996:Survival Rate; D013552:Swine; D013923:Thromboembolism / Q000209:etiology / Q000517:prevention & control*; D015912:Thrombolytic Therapy / Q000379:methods; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D013997:Time Factors
D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin; D017985:Dalteparin